Significance
The availability of in vitro human cardiomyocytes generated from induced pluripotent stem cells (iPSCs) opens the possibility to develop human in vitro heart models for disease modeling and drug testing. However, iPSC-derived cardiomyocytes remain structurally and functionally immature, which hinders their application. In this manuscript, we present an optimized and complete microfluidic system that enhances maturation of iPSC-derived cardiomyocytes through physiological cyclic pulsatile hemodynamic forces. Furthermore, we improved our microfluidic system by using a closed microfluidic recirculation and oxygen exchangers to achieve and maintain low oxygen in the culture chambers, which is suitable for mimicking the hypoxic condition and studying the pathophysiological mechanisms of human diseases in vitro. In the future, a variety of technologies including 3D tissue engineering could be integrated into our system, which may greatly extend the use of iPSC-derived cardiac models in drug development and disease modeling.
Statement of significance
The availability of in vitro human cardiomyocytes generated from induced pluripotent stem cells (iPSCs) opens the possibility to develop human in vitro heart models for disease modeling and drug testing. However, iPSC-derived cardiomyocytes remain structurally and functionally immature, which hinders their application. In this manuscript, we present an optimized and complete microfluidic system that enhances maturation of iPSC-derived cardiomyocytes through physiological cyclic pulsatile hemodynamic forces. Furthermore, we improved our microfluidic system by using a closed microfluidic recirculation and oxygen exchangers to achieve and maintain low oxygen in the culture chambers, which is suitable for mimicking the hypoxic condition and studying the pathophysiological mechanisms of human diseases in vitro. In the future, a variety of technologies including 3D tissue engineering could be integrated into our system, which may greatly extend the use of iPSC-derived cardiac models in drug development and disease modeling.